Strong PD-L1 affect clinical outcomes in advanced NSCLC treated with third-generation EGFR-TKIs.

Background: In first/second generation EGFR-TKIs, strong PD-L1 expression contributes to primary resistance, significantly affecting patient prognosis. The relationship between PD-L1 expression levels and third-generation TKIs remains unclear. Methods: This study analyzed advanced NSCLC who received third-generation EGFR-TKIs as first-line systemic therapy from March 2019 to June 2022. The EGFR and PD-L1 status of the patients was also assessed. Results: Overall, 150 patients were included in this study. PD-L1 expression was negative (PD-L1 tumor proportion score <1%) in 89 cases, weak (1–49%) in 42 cases, and strong (≥50%) in 19 cases. mPFS for patients with negative, weak and strong PD-L1 expressions was 23.60, 26.12 and 16.60 months, respectively. The mPFS for strong PD-L1 expression was significantly shorter than that for with weak PD-L1 expression but was not associated with negativity. The same conclusions were shown in subgroup analyses of mutation types and TKI kinds. In addition, Relative to PD-L1-negative patients, resistance to TKIs may be associated with early progression for patients with strong PD-L1 expression. Conclusion: PD-L1 expression in tumor cells influenced the clinical outcomes of patients with advanced NSCLC treated with third-generation EGFR-TKIs. Stronger PD-L1 expression in TKIs-treated patients with advanced first-line EGFR-mutated NSCLC was associated with worse PFS. Article highlights This retrospective study showed that strong PD-L1 expression predicts poor response to EGFR-TKIs therapy in patients with EGFR-mutated NSCLC. PD-L1 expression and the efficacy of three-generation TKIs in which the cut-off is 1 is not a better demarcator. PD-L1 expression can be used as a reliable biomarker for EGFR-TKI therapy to predict patient survival. PD-L1, as a biomarker for evaluating prognosis, will not change due to mutation and TKI types. PD-L1, as a biomarker for evaluating prognosis, is still applicable in non-classical mutations of EGFR. High expression of PD-L1 may be a predictive indicator for primary drug resistance in targeted therapy. The relationship between PD-L1 expression combined with gene co-mutation and the prognosis of third-generation TKI can be a future research direction. Exploring effective biomarkers to enrich the beneficiary population may be an important research direction for optimizing the application of immunotherapy in EGFR-TKIs-resistant NSCLC. [ABSTRACT FROM AUTHOR]